Generated: 2025-11-17 00:31:43
Total Drugs Analyzed: 23
Initial Task: BBBP
SMILES: C[C@H](C1=CC(=C(C=C1)C2=CC=CC=C2)F)C(=O)O
No valid paths found. The optimization could not generate any improved molecules.
Input SMILES: C[C@H](C1=CC(=C(C=C1)C2=CC=CC=C2)F)C(=O)O
Reason: All generated molecules had worse scores than the initial molecule.
num_beams=7 or num_beams=10 for more diversitydepth=1 to see if single-step improvements workInitial Task: BBBP
SMILES: C1=CC=C(C=C1)NC(=O)/C=C/C2=C(C(=O)O)NC3=C2C(=CC(=C3)Cl)Cl
No valid paths found. The optimization could not generate any improved molecules.
Input SMILES: C1=CC=C(C=C1)NC(=O)/C=C/C2=C(C(=O)O)NC3=C2C(=CC(=C3)Cl)Cl
Reason: All generated molecules had worse scores than the initial molecule.
num_beams=7 or num_beams=10 for more diversitydepth=1 to see if single-step improvements workInitial Task: BBBP
SMILES: CC(C)(C)/[N+](=C/C1=CC=C(C=C1S(=O)(=O)OC)S(=O)(=O)OC)/[O-]
No valid paths found. The optimization could not generate any improved molecules.
Input SMILES: CC(C)(C)/[N+](=C/C1=CC=C(C=C1S(=O)(=O)OC)S(=O)(=O)OC)/[O-]
Reason: All generated molecules had worse scores than the initial molecule.
num_beams=7 or num_beams=10 for more diversitydepth=1 to see if single-step improvements workInitial Task: HIA
SMILES: CC1=NC2=C(C(=N1)NC3=NNC4=C3CN(C(=O)N[C@H](CN(C)C)C5=CC=CC=C5)C4(C)C)SC=C2
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`CC1=NC2=C(C(=N1)NC3=NNC4=C3CN(C(=O)N[C@H](CN(C)C)C5=CC=CC=C5)C4(C)C)SC=C2`
▶ Show ADMET Scores
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**Final Optimized**
`COc1cc(-c2n[nH]c3c2CN(c2n[nH]c4c2CN(c2n[nH]c5c2CN(C(=O)N[C@@H](CN(C)C)Nc2nc(C)nc6ccsc26)C5(C)C)C4(C)C)C3(C)C)ccc1O`
▶ Show ADMET Scores
|
Optimization Steps:
DETAILSPLACEHOLDER2
After (Step 1)
Cc1nc(Nc2n[nH]c3c2CN(C(=O)N[C@@H](CN(C)C)Nc2nc(C)nc4ccsc24)C3(C)C)c2sccc2n1
QED: 0.2053 (-0.1618) ❌
Number of Blocks: 4 (+0) ➡️
Block Changes: 6 (+3, -3)
HIA Score: 0.984575 → 0.995240 (+0.010665)
DETAILSPLACEHOLDER3
**Before (Step 1)**
`Cc1nc(Nc2n[nH]c3c2CN(C(=O)N[C@@H](CN(C)C)Nc2nc(C)nc4ccsc24)C3(C)C)c2sccc2n1`
▶ All ADMET Scores
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**After (Step 2)**
`Cc1nc(N[C@H](CN(C)C)NC(=O)N2Cc3c(N4Cc5c(C(=O)Cc6cccs6)n[nH]c5C4(C)C)n[nH]c3C2(C)C)c2sccc2n1`
QED: 0.1259 (-0.0794) ❌ Number of Blocks: 5 (+1) ↑ Block Changes: 3 (+2, -1) PGP Score: 0.564487 → 0.572543 (+0.008057) DETAILSPLACEHOLDER5 |
DETAILSPLACEHOLDER6
After (Step 3)
COc1cc(-c2n[nH]c3c2CN(c2n[nH]c4c2CN(c2n[nH]c5c2CN(C(=O)N[C@@H](CN(C)C)Nc2nc(C)nc6ccsc26)C5(C)C)C4(C)C)C3(C)C)ccc1O
QED: 0.0961 (-0.0299) ❌
Number of Blocks: 6 (+1) ↑
Block Changes: 4 (+2, -2)
CYP3A4 Score: 0.004173 → 0.000889 (-0.003285)
DETAILSPLACEHOLDER7
Step 1: HIA ✅
| Original | New | Change |
|---|---|---|
| 0.984575 | 0.995240 | +0.010665 ↑ |
Cc1nc(Nc2n[nH]c3c2CN(C(=O)N[C@@H](CN(C)C)Nc2nc(C)nc4ccsc24)C3(C)C)c2sccc2n1
Step 2: PGP ⚠️
| Original | New | Change |
|---|---|---|
| 0.564487 | 0.572543 | +0.008057 ↓ |
Cc1nc(N[C@H](CN(C)C)NC(=O)N2Cc3c(N4Cc5c(C(=O)Cc6cccs6)n[nH]c5C4(C)C)n[nH]c3C2(C)C)c2sccc2n1
Step 3: CYP3A4 ✅
| Original | New | Change |
|---|---|---|
| 0.004173 | 0.000889 | -0.003285 ↓ |
COc1cc(-c2n[nH]c3c2CN(c2n[nH]c4c2CN(c2n[nH]c5c2CN(C(=O)N[C@@H](CN(C)C)Nc2nc(C)nc6ccsc26)C5(C)C)C4(C)C)C3(C)C)ccc1O
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.419049 | 0.686654 | +0.267605 | -0.6386 | +63.86% | ❌ Declined |
| BBBP | ↑ higher | 0.778013 | 0.000213 | -0.777801 | -0.9997 | -99.97% | ❌ Declined |
| CYP3A4 | ↓ lower | 0.011948 | 0.000889 | -0.011059 | +0.9256 | -92.56% | ✅ Improved |
| DILI | ↓ lower | 0.793920 | 0.659112 | -0.134808 | +0.1698 | -16.98% | ✅ Improved |
| HIA | ↑ higher | 0.984575 | 0.997891 | +0.013316 | +0.0135 | +1.35% | ✅ Improved |
| PGP | ↓ lower | 0.499705 | 0.556859 | +0.057154 | -0.1144 | +11.44% | ❌ Declined |
Improved: 3/6 (50.0%) | Molecules: 139 | Paths: 2743
Status: 2/6 meet thresholds
⚠️ Below threshold: 4
| Task | Score | Threshold | Gap |
|---|---|---|---|
| BBBP | 0.0002 | ↑ 0.5 | 0.4998 |
| AMES | 0.6867 | ↓ 0.3 | 0.3867 |
| DILI | 0.6591 | ↓ 0.4 | 0.2591 |
| PGP | 0.5569 | ↓ 0.3 | 0.2569 |
✅ Passing: 2
| Task | Score | Threshold |
|---|---|---|
| CYP3A4 | 0.0009 | ↓ 0.55 |
| HIA | 0.9979 | ↑ 0.2 |
Initial Task: HIA
SMILES: C1=CC2=C(C=C1)NC(=O)N(C2)C3CCN(CC3)C(=O)N[C@H](CC4=CC(=C(C(=C4)Br)O)Br)C(=O)N[C@@H](CCCCN)C(=O)N5CCN(CC5)C6=CC=NC=C6
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`C1=CC2=C(C=C1)NC(=O)N(C2)C3CCN(CC3)C(=O)N[C@H](CC4=CC(=C(C(=C4)Br)O)Br)C(=O)N[C@@H](CCCCN)C(=O)N5CCN(CC5)C6=CC=NC=C6`
▶ Show ADMET Scores
|
**Final Optimized**
`CC1(C)c2[nH]nc(N[C@H](Cc3cc(Br)c(O)c(Br)c3)C(=O)N3Cc4c(N[C@H](Cc5cc(Br)c(O)c(Br)c5)C(=O)C(=O)/C=C/c5c(C(=O)O)[nH]c6cc(Cl)cc(Cl)c56)n[nH]c4C3(C)C)c2CN1C(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NC(=O)N1CCC(N2Cc3ccccc3NC2=O)CC1`
▶ Show ADMET Scores
|
Optimization Steps:
DETAILSPLACEHOLDER10
After (Step 1)
CC(C)CCOc1n[nH]c2c1CN(C(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NC(=O)N1CCC(N3Cc4ccccc4NC3=O)CC1)C2(C)C
QED: 0.0420 (-0.1246) ❌
Number of Blocks: 6 (+1) ↑
Block Changes: 8 (+4, -4)
HIA Score: 0.989571 → 0.999710 (+0.010140)
DETAILSPLACEHOLDER11
DETAILSPLACEHOLDER12
After (Step 2)
CCCCC(CC)COC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)Nc1n[nH]c2c1CN(C(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NC(=O)N1CCC(N3Cc4ccccc4NC3=O)CC1)C2(C)C
QED: 0.0182 (-0.0238) ❌
Number of Blocks: 7 (+1) ↑
Block Changes: 3 (+2, -1)
AMES Score: 0.612386 → 0.564568 (-0.047817)
DETAILSPLACEHOLDER13
DETAILSPLACEHOLDER14
After (Step 3)
CC1(C)c2[nH]nc(N[C@H](Cc3cc(Br)c(O)c(Br)c3)C(=O)N3Cc4c(N[C@H](Cc5cc(Br)c(O)c(Br)c5)C(=O)C(=O)/C=C/c5c(C(=O)O)[nH]c6cc(Cl)cc(Cl)c56)n[nH]c4C3(C)C)c2CN1C(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NC(=O)N1CCC(N2Cc3ccccc3NC2=O)CC1
QED: 0.0265 (+0.0083) ✅
Number of Blocks: 7 (+0) ➡️
Block Changes: 5 (+2, -3)
CYP3A4 Score: 0.000019 → 0.000009 (-0.000011)
DETAILSPLACEHOLDER15
Step 1: HIA ✅
| Original | New | Change |
|---|---|---|
| 0.989571 | 0.999710 | +0.010140 ↑ |
CC(C)CCOc1n[nH]c2c1CN(C(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NC(=O)N1CCC(N3Cc4ccccc4NC3=O)CC1)C2(C)C
Step 2: AMES ✅
| Original | New | Change |
|---|---|---|
| 0.612386 | 0.564568 | -0.047817 ↓ |
CCCCC(CC)COC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)Nc1n[nH]c2c1CN(C(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NC(=O)N1CCC(N3Cc4ccccc4NC3=O)CC1)C2(C)C
Step 3: CYP3A4 ✅
| Original | New | Change |
|---|---|---|
| 0.000019 | 0.000009 | -0.000011 ↓ |
CC1(C)c2[nH]nc(N[C@H](Cc3cc(Br)c(O)c(Br)c3)C(=O)N3Cc4c(N[C@H](Cc5cc(Br)c(O)c(Br)c5)C(=O)C(=O)/C=C/c5c(C(=O)O)[nH]c6cc(Cl)cc(Cl)c56)n[nH]c4C3(C)C)c2CN1C(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NC(=O)N1CCC(N2Cc3ccccc3NC2=O)CC1
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.721609 | 0.528857 | -0.192753 | +0.2671 | -26.71% | ✅ Improved |
| BBBP | ↑ higher | 0.000066 | 0.000205 | +0.000139 | +2.1037 | +210.37% | ✅ Improved |
| CYP3A4 | ↓ lower | 0.009376 | 0.000009 | -0.009367 | +0.9991 | -99.91% | ✅ Improved |
| DILI | ↓ lower | 0.714050 | 0.525996 | -0.188054 | +0.2634 | -26.34% | ✅ Improved |
| HIA | ↑ higher | 0.989571 | 0.999984 | +0.010413 | +0.0105 | +1.05% | ✅ Improved |
| PGP | ↓ lower | 0.702944 | 0.824368 | +0.121425 | -0.1727 | +17.27% | ❌ Declined |
Improved: 5/6 (83.3%) | Molecules: 637 | Paths: 5011
Status: 2/6 meet thresholds
⚠️ Below threshold: 4
| Task | Score | Threshold | Gap |
|---|---|---|---|
| PGP | 0.8244 | ↓ 0.3 | 0.5244 |
| BBBP | 0.0002 | ↑ 0.5 | 0.4998 |
| AMES | 0.5289 | ↓ 0.3 | 0.2289 |
| DILI | 0.5260 | ↓ 0.4 | 0.1260 |
✅ Passing: 2
| Task | Score | Threshold |
|---|---|---|
| CYP3A4 | 0.0000 | ↓ 0.55 |
| HIA | 1.0000 | ↑ 0.2 |
Initial Task: HIA
SMILES: CC(=O)OC[C@H](COC1=CC=C(C=C1)C(C)(C)C2=CC=C(C=C2)OC[C@@H](CCl)OC(=O)C)OC(=O)C
No valid paths found. The optimization could not generate any improved molecules.
Input SMILES: CC(=O)OC[C@H](COC1=CC=C(C=C1)C(C)(C)C2=CC=C(C=C2)OC[C@@H](CCl)OC(=O)C)OC(=O)C
Reason: All generated molecules had worse scores than the initial molecule.
num_beams=7 or num_beams=10 for more diversitydepth=1 to see if single-step improvements workInitial Task: HIA
SMILES: C1=CC(=NC=C1/C=C/C(=O)NCC2=CC3=C(C(=CC(=C3)C4=CC=C(C=C4)C(=O)N5CCC(CC5)(F)F)C6=CC=C(C=C6)F)O2)N
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`C1=CC(=NC=C1/C=C/C(=O)NCC2=CC3=C(C(=CC(=C3)C4=CC=C(C=C4)C(=O)N5CCC(CC5)(F)F)C6=CC=C(C=C6)F)O2)N`
▶ Show ADMET Scores
|
**Final Optimized**
`CC(=O)OC[C@H](CON1Cc2c(-c3cn(C)c4ccccc34)n[nH]c2C1(C)C)OC(C)=O`
▶ Show ADMET Scores
|
Optimization Steps:
DETAILSPLACEHOLDER18
After (Step 1)
CC(=O)OC[C@H](CONCc1cc2cc(-c3ccc(C(C)(C)c4ccc(N5CCC(F)(F)CC5)cc4)cc3)cc(-c3ccc(F)cc3)c2o1)OC(C)=O
QED: 0.0731 (-0.1188) ❌
Number of Blocks: 4 (+0) ➡️
Block Changes: 6 (+3, -3)
HIA Score: 0.988937 → 0.941353 (-0.047584)
DETAILSPLACEHOLDER19
DETAILSPLACEHOLDER20
After (Step 2)
CC(=O)OC[C@H](COC(=O)/C=C/c1c(C(=O)O)[nH]c2cc(Cl)cc(Cl)c12)OC(C)=O
QED: 0.3503 (+0.2772) ✅
Number of Blocks: 2 (-2) ↓
Block Changes: 6 (+2, -4)
AMES Score: 0.432780 → 0.408373 (-0.024407)
DETAILSPLACEHOLDER21
DETAILSPLACEHOLDER22
After (Step 3)
CC(=O)OC[C@H](CON1Cc2c(-c3cn(C)c4ccccc34)n[nH]c2C1(C)C)OC(C)=O
QED: 0.5639 (+0.2137) ✅
Number of Blocks: 2 (+0) ➡️
Block Changes: 4 (+2, -2)
AMES Score: 0.408373 → 0.381034 (-0.027339)
DETAILSPLACEHOLDER23
Step 1: HIA ⚠️
| Original | New | Change |
|---|---|---|
| 0.988937 | 0.941353 | -0.047584 ↑ |
CC(=O)OC[C@H](CONCc1cc2cc(-c3ccc(C(C)(C)c4ccc(N5CCC(F)(F)CC5)cc4)cc3)cc(-c3ccc(F)cc3)c2o1)OC(C)=O
Step 2: AMES ✅
| Original | New | Change |
|---|---|---|
| 0.432780 | 0.408373 | -0.024407 ↓ |
CC(=O)OC[C@H](COC(=O)/C=C/c1c(C(=O)O)[nH]c2cc(Cl)cc(Cl)c12)OC(C)=O
Step 3: AMES ✅
| Original | New | Change |
|---|---|---|
| 0.408373 | 0.381034 | -0.027339 ↓ |
CC(=O)OC[C@H](CON1Cc2c(-c3cn(C)c4ccccc34)n[nH]c2C1(C)C)OC(C)=O
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.438620 | 0.381034 | -0.057586 | +0.1313 | -13.13% | ✅ Improved |
| BBBP | ↑ higher | 0.999970 | 1.000000 | +0.000030 | +0.0000 | +0.00% | ✅ Improved |
| CYP3A4 | ↓ lower | 0.046397 | 0.011194 | -0.035203 | +0.7587 | -75.87% | ✅ Improved |
| DILI | ↓ lower | 0.750240 | 0.458021 | -0.292219 | +0.3895 | -38.95% | ✅ Improved |
| HIA | ↑ higher | 0.988937 | 0.995235 | +0.006298 | +0.0064 | +0.64% | ✅ Improved |
| PGP | ↓ lower | 0.653441 | 0.630667 | -0.022773 | +0.0349 | -3.49% | ✅ Improved |
Improved: 6/6 (100.0%) | Molecules: 175 | Paths: 1473
Status: 3/6 meet thresholds
⚠️ Below threshold: 3
| Task | Score | Threshold | Gap |
|---|---|---|---|
| PGP | 0.6307 | ↓ 0.3 | 0.3307 |
| AMES | 0.3810 | ↓ 0.3 | 0.0810 |
| DILI | 0.4580 | ↓ 0.4 | 0.0580 |
✅ Passing: 3
| Task | Score | Threshold |
|---|---|---|
| BBBP | 1.0000 | ↑ 0.5 |
| CYP3A4 | 0.0112 | ↓ 0.55 |
| HIA | 0.9952 | ↑ 0.2 |
Initial Task: HIA
SMILES: C(CCOC1=C(C=O)C(=CC=C1)O)CC(=O)O
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`C(CCOC1=C(C=O)C(=CC=C1)O)CC(=O)O`
▶ Step 1: HIA (+0.0107 ↑) ✅
DETAILSPLACEHOLDER28 |
After (Step 2)
QED: 0.7458 (+0.5340) ✅ Number of Blocks: 2 (+1) ↑ Block Changes: 3 (+2, -1) AMES Score: 0.428290 → 0.776573 (+0.348283) DETAILSPLACEHOLDER29 |
DETAILSPLACEHOLDER30
After (Step 3)
CC1(C)c2[nH]nc(N3Cc4c(C(=O)c5cccs5)n[nH]c4C3(C)C)c2CN1OCCCCC(=O)O
QED: 0.2992 (-0.4465) ❌
Number of Blocks: 2 (+0) ➡️
Block Changes: 2 (+1, -1)
PGP Score: 0.609776 → 0.498713 (-0.111063)
DETAILSPLACEHOLDER31
Step 1: HIA ✅
| Original | New | Change |
|---|---|---|
| 0.984511 | 0.999700 | +0.015189 ↑ |
CC(=O)O[C@H](CCl)COOCCCCC(=O)O
Step 2: AMES ⚠️
| Original | New | Change |
|---|---|---|
| 0.428290 | 0.776573 | +0.348283 ↓ |
Cc1nc(-c2n[nH]c3c2CN(OCCCCC(=O)O)C3(C)C)cs1
Step 3: PGP ✅
| Original | New | Change |
|---|---|---|
| 0.609776 | 0.498713 | -0.111063 ↓ |
CC1(C)c2[nH]nc(N3Cc4c(C(=O)c5cccs5)n[nH]c4C3(C)C)c2CN1OCCCCC(=O)O
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.687406 | 0.368299 | -0.319107 | +0.4642 | -46.42% | ✅ Improved |
| BBBP | ↑ higher | 0.001264 | 0.898326 | +0.897062 | +709.5506 | +70955.06% | ✅ Improved |
| CYP3A4 | ↓ lower | 0.022560 | 0.005592 | -0.016969 | +0.7521 | -75.21% | ✅ Improved |
| DILI | ↓ lower | 0.623776 | 0.676924 | +0.053148 | -0.0852 | +8.52% | ❌ Declined |
| HIA | ↑ higher | 0.984511 | 0.980476 | -0.004035 | -0.0041 | -0.41% | ❌ Declined |
| PGP | ↓ lower | 0.615759 | 0.498713 | -0.117046 | +0.1901 | -19.01% | ✅ Improved |
Improved: 4/6 (66.7%) | Molecules: 85 | Paths: 1719
Status: 3/6 meet thresholds
⚠️ Below threshold: 3
| Task | Score | Threshold | Gap |
|---|---|---|---|
| DILI | 0.6769 | ↓ 0.4 | 0.2769 |
| PGP | 0.4987 | ↓ 0.3 | 0.1987 |
| AMES | 0.3683 | ↓ 0.3 | 0.0683 |
✅ Passing: 3
| Task | Score | Threshold |
|---|---|---|
| BBBP | 0.8983 | ↑ 0.5 |
| CYP3A4 | 0.0056 | ↓ 0.55 |
| HIA | 0.9805 | ↑ 0.2 |
Initial Task: DILI
SMILES: C1=C(C(=O)NC(=O)N1[C@H]2[C@H]([C@@H]([C@@H](CO)O2)O)F)I
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`C1=C(C(=O)NC(=O)N1[C@H]2[C@H]([C@@H]([C@@H](CO)O2)O)F)I`
▶ All ADMET Scores
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**Final Optimized**
`CC/C=C\CC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)Nc1n[nH]c2c1CN(OC[C@@H](CCl)OC(C)=O)C2(C)C`
▶ All ADMET Scores
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Optimization Steps:
DETAILSPLACEHOLDER34
After (Step 1)
CC(=O)O[C@H](CCl)COc1cn(C)c2ccccc12
QED: 0.6249 (+0.0629) ✅
Number of Blocks: 2 (+1) ↑
Block Changes: 3 (+2, -1)
DILI Score: 0.145744 → 0.641619 (+0.495875)
DETAILSPLACEHOLDER35
DETAILSPLACEHOLDER36
After (Step 2)
CC(=O)O[C@H](CCl)CON1Cc2c(-c3ccc(C)s3)n[nH]c2C1(C)C
QED: 0.6094 (-0.0155) ❌
Number of Blocks: 2 (+0) ➡️
Block Changes: 4 (+2, -2)
CYP3A4 Score: 0.159087 → 0.009106 (-0.149981)
DETAILSPLACEHOLDER37
DETAILSPLACEHOLDER38
After (Step 3)
CC/C=C\CC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)Nc1n[nH]c2c1CN(OC[C@@H](CCl)OC(C)=O)C2(C)C
QED: 0.1398 (-0.4696) ❌
Number of Blocks: 3 (+1) ↑
Block Changes: 3 (+2, -1)
DILI Score: 0.576163 → 0.259323 (-0.316840)
DETAILSPLACEHOLDER39
Step 1: DILI ⚠️
| Original | New | Change |
|---|---|---|
| 0.145744 | 0.641619 | +0.495875 ↓ |
CC(=O)O[C@H](CCl)COc1cn(C)c2ccccc12
Step 2: CYP3A4 ✅
| Original | New | Change |
|---|---|---|
| 0.159087 | 0.009106 | -0.149981 ↓ |
CC(=O)O[C@H](CCl)CON1Cc2c(-c3ccc(C)s3)n[nH]c2C1(C)C
Step 3: DILI ✅
| Original | New | Change |
|---|---|---|
| 0.576163 | 0.259323 | -0.316840 ↓ |
CC/C=C\CC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)Nc1n[nH]c2c1CN(OC[C@@H](CCl)OC(C)=O)C2(C)C
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.114162 | 0.266793 | +0.152631 | -1.3370 | +133.70% | ❌ Declined |
| BBBP | ↑ higher | 1.000000 | 1.000000 | +0.000000 | +0.0000 | +0.00% | ➡️ Unchanged |
| CYP3A4 | ↓ lower | 0.000000 | 0.000067 | +0.000067 | -5806.1212 | +580612.12% | ❌ Declined |
| DILI | ↓ lower | 0.145744 | 0.259323 | +0.113579 | -0.7793 | +77.93% | ❌ Declined |
| HIA | ↑ higher | 1.000000 | 0.999987 | -0.000013 | -0.0000 | -0.00% | ❌ Declined |
| PGP | ↓ lower | 0.940474 | 0.866124 | -0.074351 | +0.0791 | -7.91% | ✅ Improved |
Improved: 1/6 (16.7%) | Molecules: 271 | Paths: 19870
Status: 5/6 meet thresholds
⚠️ Below threshold: 1
| Task | Score | Threshold | Gap |
|---|---|---|---|
| PGP | 0.8661 | ↓ 0.3 | 0.5661 |
✅ Passing: 5
| Task | Score | Threshold |
|---|---|---|
| AMES | 0.2668 | ↓ 0.3 |
| BBBP | 1.0000 | ↑ 0.5 |
| CYP3A4 | 0.0001 | ↓ 0.55 |
| DILI | 0.2593 | ↓ 0.4 |
| HIA | 1.0000 | ↑ 0.2 |
Initial Task: DILI
SMILES: CCOC(=O)CN[C@H](C1CCCCC1)C(=O)N2CC[C@H]2C(=O)NCC3=CC=C(C=C3)/C(=N\O)/N
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`CCOC(=O)CN[C@H](C1CCCCC1)C(=O)N2CC[C@H]2C(=O)NCC3=CC=C(C=C3)/C(=N\O)/N`
▶ Step 2: PGP (+0.0081 ↓) ➡️
DETAILSPLACEHOLDER44 |
After (Step 2)
QED: 0.4934 (+0.2138) ✅ Number of Blocks: 4 (+1) ↑ Block Changes: 3 (+2, -1) AMES Score: 0.340648 → 0.732660 (+0.392012) DETAILSPLACEHOLDER45 |
DETAILSPLACEHOLDER46
After (Step 3)
CC(=O)OC[C@H](CON1CC[C@H]1C(=O)N1Cc2c(-c3ccc([C@@H](C)C(=O)O)cc3F)n[nH]c2C1(C)C)OC(C)=O
QED: 0.4148 (-0.0787) ❌
Number of Blocks: 3 (-1) ↓
Block Changes: 5 (+2, -3)
AMES Score: 0.732660 → 0.404659 (-0.328000)
DETAILSPLACEHOLDER47
Step 1: DILI ✅
| Original | New | Change |
|---|---|---|
| 0.649647 | 0.419199 | -0.230448 ↓ |
CCOC(=O)CN[C@@H](C(=O)N1CC[C@H]1C(=O)OC[C@@H](CCl)OC(C)=O)C1CCCCC1
Step 2: AMES ⚠️
| Original | New | Change |
|---|---|---|
| 0.340648 | 0.732660 | +0.392012 ↓ |
CCOC(=O)CN[C@@H](C(=O)N1CC[C@H]1C(=O)N1Cc2c(-c3ccc(C)s3)n[nH]c2C1(C)C)C1CCCCC1
Step 3: AMES ✅
| Original | New | Change |
|---|---|---|
| 0.732660 | 0.404659 | -0.328000 ↓ |
CC(=O)OC[C@H](CON1CC[C@H]1C(=O)N1Cc2c(-c3ccc([C@@H](C)C(=O)O)cc3F)n[nH]c2C1(C)C)OC(C)=O
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.720076 | 0.404659 | -0.315416 | +0.4380 | -43.80% | ✅ Improved |
| BBBP | ↑ higher | 0.000080 | 0.999947 | +0.999867 | +12529.0183 | +1252901.83% | ✅ Improved |
| CYP3A4 | ↓ lower | 0.018008 | 0.020061 | +0.002053 | -0.1140 | +11.40% | ❌ Declined |
| DILI | ↓ lower | 0.649647 | 0.408363 | -0.241285 | +0.3714 | -37.14% | ✅ Improved |
| HIA | ↑ higher | 0.997815 | 0.991177 | -0.006638 | -0.0067 | -0.67% | ❌ Declined |
| PGP | ↓ lower | 0.655136 | 0.659510 | +0.004374 | -0.0067 | +0.67% | ❌ Declined |
Improved: 3/6 (50.0%) | Molecules: 283 | Paths: 3915
Status: 3/6 meet thresholds
⚠️ Below threshold: 3
| Task | Score | Threshold | Gap |
|---|---|---|---|
| PGP | 0.6595 | ↓ 0.3 | 0.3595 |
| AMES | 0.4047 | ↓ 0.3 | 0.1047 |
| DILI | 0.4084 | ↓ 0.4 | 0.0084 |
✅ Passing: 3
| Task | Score | Threshold |
|---|---|---|
| BBBP | 0.9999 | ↑ 0.5 |
| CYP3A4 | 0.0201 | ↓ 0.55 |
| HIA | 0.9912 | ↑ 0.2 |
Initial Task: DILI
SMILES: CC1=C(C(=CC(=C1)OCCCS(=O)(=O)C)C)C2=CC(=CC=C2)COC3=CC=C4[C@@H](CC(=O)O)COC4=C3
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`CC1=C(C(=CC(=C1)OCCCS(=O)(=O)C)C)C2=CC(=CC=C2)COC3=CC=C4[C@@H](CC(=O)O)COC4=C3`
▶ Step 2: PGP (+0.0081 ↓) ➡️
DETAILSPLACEHOLDER52 |
After (Step 2)
QED: 0.0632 (-0.0365) ❌ Number of Blocks: 4 (+1) ↑ Block Changes: 5 (+3, -2) BBBP Score: 0.999996 → 1.000000 (+0.000004) DETAILSPLACEHOLDER53 |
DETAILSPLACEHOLDER54
After (Step 3)
Cc1cc(N2Cc3c(N4Cc5c(C(=O)Cc6cccs6)n[nH]c5C4(C)C)n[nH]c3C2(C)C)cc(C)c1C(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NCOc1ccc2c(c1)OC[C@@H]2CC(=O)O
QED: 0.0486 (-0.0146) ❌
Number of Blocks: 5 (+1) ↑
Block Changes: 1 (+1, -0)
PGP Score: 0.798334 → 0.755818 (-0.042516)
DETAILSPLACEHOLDER55
Step 1: DILI ✅
| Original | New | Change |
|---|---|---|
| 0.605552 | 0.424327 | -0.181224 ↓ |
Cc1cc(OCCCS(C)(=O)=O)cc(C)c1C(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NCOc1ccc2c(c1)OC[C@@H]2CC(=O)O
Step 2: BBBP ✅
| Original | New | Change |
|---|---|---|
| 0.999996 | 1.000000 | +0.000004 ↑ |
Cc1cc(N2Cc3c(C(=O)Cc4cccs4)n[nH]c3C2(C)C)cc(C)c1C(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NCOc1ccc2c(c1)OC[C@@H]2CC(=O)O
Step 3: PGP ✅
| Original | New | Change |
|---|---|---|
| 0.798334 | 0.755818 | -0.042516 ↓ |
Cc1cc(N2Cc3c(N4Cc5c(C(=O)Cc6cccs6)n[nH]c5C4(C)C)n[nH]c3C2(C)C)cc(C)c1C(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NCOc1ccc2c(c1)OC[C@@H]2CC(=O)O
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.459273 | 0.259236 | -0.200037 | +0.4356 | -43.56% | ✅ Improved |
| BBBP | ↑ higher | 0.999996 | 0.999966 | -0.000030 | -0.0000 | -0.00% | ❌ Declined |
| CYP3A4 | ↓ lower | 0.082408 | 0.001861 | -0.080547 | +0.9774 | -97.74% | ✅ Improved |
| DILI | ↓ lower | 0.605552 | 0.380775 | -0.224777 | +0.3712 | -37.12% | ✅ Improved |
| HIA | ↑ higher | 0.659498 | 0.996015 | +0.336517 | +0.5103 | +51.03% | ✅ Improved |
| PGP | ↓ lower | 0.636196 | 0.755818 | +0.119622 | -0.1880 | +18.80% | ❌ Declined |
Improved: 4/6 (66.7%) | Molecules: 175 | Paths: 2055
Status: 5/6 meet thresholds
⚠️ Below threshold: 1
| Task | Score | Threshold | Gap |
|---|---|---|---|
| PGP | 0.7558 | ↓ 0.3 | 0.4558 |
✅ Passing: 5
| Task | Score | Threshold |
|---|---|---|
| AMES | 0.2592 | ↓ 0.3 |
| BBBP | 1.0000 | ↑ 0.5 |
| CYP3A4 | 0.0019 | ↓ 0.55 |
| DILI | 0.3808 | ↓ 0.4 |
| HIA | 0.9960 | ↑ 0.2 |
Initial Task: DILI
SMILES: CC(=O)OCC(C)(C)CN1C2=CC=C(C=C2[C@@H](C3=CC=CC(=C3OC)OC)O[C@H](CC(=O)N4CCC(CC4)CC(=O)O)C1=O)Cl
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`CC(=O)OCC(C)(C)CN1C2=CC=C(C=C2[C@@H](C3=CC=CC(=C3OC)OC)O[C@H](CC(=O)N4CCC(CC4)CC(=O)O)C1=O)Cl`
▶ All ADMET Scores
|
**Final Optimized**
`CC(C)CC(=O)c1n[nH]c2c1CN(c1n[nH]c3c1CN(c1n[nH]c4c1CN(NCc1ccc(/C(N)=N\O)cc1)C4(C)C)C3(C)C)C2(C)C`
▶ All ADMET Scores
|
Optimization Steps:
DETAILSPLACEHOLDER58
After (Step 1)
CC(=O)OCC(C)(C)CN1C(=O)[C@@H](CC(=O)NCc2ccc(/C(N)=N\O)cc2)O[C@@H](N2Cc3c(OCC(C)C)n[nH]c3C2(C)C)c2cc(Cl)ccc21
QED: 0.0614 (-0.2789) ❌
Number of Blocks: 2 (-1) ↓
Block Changes: 5 (+2, -3)
DILI Score: 0.602326 → 0.416277 (-0.186049)
DETAILSPLACEHOLDER59
DETAILSPLACEHOLDER60
After (Step 2)
CC(=O)OC[C@H](COc1n[nH]c2c1CN(c1n[nH]c3c1CN(NCc1ccc(/C(N)=N\O)cc1)C3(C)C)C2(C)C)OC(C)=O
QED: 0.0699 (+0.0085) ✅
Number of Blocks: 4 (+2) ↑
Block Changes: 6 (+4, -2)
CYP3A4 Score: 0.050735 → 0.020237 (-0.030498)
DETAILSPLACEHOLDER61
DETAILSPLACEHOLDER62
After (Step 3)
CC(C)CC(=O)c1n[nH]c2c1CN(c1n[nH]c3c1CN(c1n[nH]c4c1CN(NCc1ccc(/C(N)=N\O)cc1)C4(C)C)C3(C)C)C2(C)C
QED: 0.0496 (-0.0203) ❌
Number of Blocks: 4 (+0) ➡️
Block Changes: 2 (+1, -1)
CYP3A4 Score: 0.020237 → 0.001016 (-0.019221)
DETAILSPLACEHOLDER63
Step 1: DILI ✅
| Original | New | Change |
|---|---|---|
| 0.602326 | 0.416277 | -0.186049 ↓ |
CC(=O)OCC(C)(C)CN1C(=O)[C@@H](CC(=O)NCc2ccc(/C(N)=N\O)cc2)O[C@@H](N2Cc3c(OCC(C)C)n[nH]c3C2(C)C)c2cc(Cl)ccc21
Step 2: CYP3A4 ✅
| Original | New | Change |
|---|---|---|
| 0.050735 | 0.020237 | -0.030498 ↓ |
CC(=O)OC[C@H](COc1n[nH]c2c1CN(c1n[nH]c3c1CN(NCc1ccc(/C(N)=N\O)cc1)C3(C)C)C2(C)C)OC(C)=O
Step 3: CYP3A4 ✅
| Original | New | Change |
|---|---|---|
| 0.020237 | 0.001016 | -0.019221 ↓ |
CC(C)CC(=O)c1n[nH]c2c1CN(c1n[nH]c3c1CN(c1n[nH]c4c1CN(NCc1ccc(/C(N)=N\O)cc1)C4(C)C)C3(C)C)C2(C)C
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.419620 | 0.683061 | +0.263441 | -0.6278 | +62.78% | ❌ Declined |
| BBBP | ↑ higher | 0.999985 | 0.000186 | -0.999799 | -0.9998 | -99.98% | ❌ Declined |
| CYP3A4 | ↓ lower | 0.035988 | 0.001016 | -0.034972 | +0.9718 | -97.18% | ✅ Improved |
| DILI | ↓ lower | 0.602326 | 0.619393 | +0.017067 | -0.0283 | +2.83% | ❌ Declined |
| HIA | ↑ higher | 0.980337 | 0.987780 | +0.007443 | +0.0076 | +0.76% | ✅ Improved |
| PGP | ↓ lower | 0.662407 | 0.592538 | -0.069869 | +0.1055 | -10.55% | ✅ Improved |
Improved: 3/6 (50.0%) | Molecules: 415 | Paths: 7886
Status: 2/6 meet thresholds
⚠️ Below threshold: 4
| Task | Score | Threshold | Gap |
|---|---|---|---|
| BBBP | 0.0002 | ↑ 0.5 | 0.4998 |
| AMES | 0.6831 | ↓ 0.3 | 0.3831 |
| PGP | 0.5925 | ↓ 0.3 | 0.2925 |
| DILI | 0.6194 | ↓ 0.4 | 0.2194 |
✅ Passing: 2
| Task | Score | Threshold |
|---|---|---|
| CYP3A4 | 0.0010 | ↓ 0.55 |
| HIA | 0.9878 | ↑ 0.2 |
Initial Task: DILI
SMILES: C1=CC(=NC(=C1)OCC2=CC=C(C=C2F)C#N)C3CCN(CC3)CC4=NC5=CC=C(C=C5N4C[C@@H]6CCO6)C(=O)O
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`C1=CC(=NC(=C1)OCC2=CC=C(C=C2F)C#N)C3CCN(CC3)CC4=NC5=CC=C(C=C5N4C[C@@H]6CCO6)C(=O)O`
▶ Step 3: CYP3A4 (-0.0033 ↓) ✅
DETAILSPLACEHOLDER68 |
After (Step 2)
QED: 0.1586 (-0.1151) ❌ Number of Blocks: 5 (+1) ↑ Block Changes: 7 (+4, -3) PGP Score: 0.598865 → 0.554803 (-0.044061) DETAILSPLACEHOLDER69 |
DETAILSPLACEHOLDER70
After (Step 3)
Cc1cc(N2Cc3c(N4Cc5c(-c6c(C)cc(NC78CC9CC(CC(C9)C7)C8)cc6C)n[nH]c5C4(C)C)n[nH]c3C2(C)C)cc(C)c1-c1cccc(OCc2ccc(C#N)cc2F)n1
QED: 0.1314 (-0.0272) ❌
Number of Blocks: 7 (+2) ↑
Block Changes: 3 (+2, -1)
PGP Score: 0.554803 → 0.571472 (+0.016669)
DETAILSPLACEHOLDER71
Step 1: DILI ✅
| Original | New | Change |
|---|---|---|
| 0.804817 | 0.721803 | -0.083013 ↓ |
COc1ccc(-c2n[nH]c3c2CN(CN2CCC(c4cccc(OCc5ccc(C#N)cc5F)n4)CC2)C3(C)C)cc1O
Step 2: PGP ✅
| Original | New | Change |
|---|---|---|
| 0.598865 | 0.554803 | -0.044061 ↓ |
CC1(C)c2[nH]nc(N3Cc4c(NC56CC7CC(CC(C7)C5)C6)n[nH]c4C3(C)C)c2CN1CN1CCC(c2cccc(OCc3ccc(C#N)cc3F)n2)CC1
Step 3: PGP ⚠️
| Original | New | Change |
|---|---|---|
| 0.554803 | 0.571472 | +0.016669 ↓ |
Cc1cc(N2Cc3c(N4Cc5c(-c6c(C)cc(NC78CC9CC(CC(C9)C7)C8)cc6C)n[nH]c5C4(C)C)n[nH]c3C2(C)C)cc(C)c1-c1cccc(OCc2ccc(C#N)cc2F)n1
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.755845 | 0.648178 | -0.107668 | +0.1424 | -14.24% | ✅ Improved |
| BBBP | ↑ higher | 0.000238 | 0.000290 | +0.000053 | +0.2221 | +22.21% | ✅ Improved |
| CYP3A4 | ↓ lower | 0.009860 | 0.001107 | -0.008752 | +0.8877 | -88.77% | ✅ Improved |
| DILI | ↓ lower | 0.804817 | 0.550500 | -0.254317 | +0.3160 | -31.60% | ✅ Improved |
| HIA | ↑ higher | 0.993762 | 0.966419 | -0.027343 | -0.0275 | -2.75% | ❌ Declined |
| PGP | ↓ lower | 0.573991 | 0.571472 | -0.002519 | +0.0044 | -0.44% | ✅ Improved |
Improved: 5/6 (83.3%) | Molecules: 385 | Paths: 5311
Status: 2/6 meet thresholds
⚠️ Below threshold: 4
| Task | Score | Threshold | Gap |
|---|---|---|---|
| BBBP | 0.0003 | ↑ 0.5 | 0.4997 |
| AMES | 0.6482 | ↓ 0.3 | 0.3482 |
| PGP | 0.5715 | ↓ 0.3 | 0.2715 |
| DILI | 0.5505 | ↓ 0.4 | 0.1505 |
✅ Passing: 2
| Task | Score | Threshold |
|---|---|---|
| CYP3A4 | 0.0011 | ↓ 0.55 |
| HIA | 0.9664 | ↑ 0.2 |
Initial Task: BBBP
SMILES: CN(CCOC1=CC=C(C=C1)CC2C(=O)NC(=O)S2)C3=CC=CC=N3
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`CN(CCOC1=CC=C(C=C1)CC2C(=O)NC(=O)S2)C3=CC=CC=N3`
▶ All ADMET Scores
|
**Final Optimized**
`CCCCCCC(CCCC)COC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)Nc1n[nH]c2c1CN(N(C)CCOC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NCC1SC(=O)NC1=O)C2(C)C`
▶ All ADMET Scores
|
Optimization Steps:
DETAILSPLACEHOLDER74
After (Step 1)
CCCCC(CC)COc1n[nH]c2c1CN(N(C)CCOC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NCC1SC(=O)NC1=O)C2(C)C
QED: 0.1564 (-0.6645) ❌
Number of Blocks: 4 (+0) ➡️
Block Changes: 8 (+4, -4)
BBBP Score: 0.646056 → 0.000386 (-0.645670)
DETAILSPLACEHOLDER75
DETAILSPLACEHOLDER76
After (Step 2)
CCCCC(CC)COC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)Nc1n[nH]c2c1CN(N(C)CCOC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NCC1SC(=O)NC1=O)C2(C)C
QED: 0.0569 (-0.0995) ❌
Number of Blocks: 5 (+1) ↑
Block Changes: 5 (+3, -2)
AMES Score: 0.587563 → 0.499352 (-0.088211)
DETAILSPLACEHOLDER77
DETAILSPLACEHOLDER78
After (Step 3)
CCCCCCC(CCCC)COC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)Nc1n[nH]c2c1CN(N(C)CCOC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NCC1SC(=O)NC1=O)C2(C)C
QED: 0.0186 (-0.0383) ❌
Number of Blocks: 6 (+1) ↑
Block Changes: 2 (+1, -1)
CYP3A4 Score: 0.000004 → 0.000001 (-0.000004)
DETAILSPLACEHOLDER79
Step 1: BBBP ⚠️
| Original | New | Change |
|---|---|---|
| 0.646056 | 0.000386 | -0.645670 ↑ |
CCCCC(CC)COc1n[nH]c2c1CN(N(C)CCOC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NCC1SC(=O)NC1=O)C2(C)C
Step 2: AMES ✅
| Original | New | Change |
|---|---|---|
| 0.587563 | 0.499352 | -0.088211 ↓ |
CCCCC(CC)COC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)Nc1n[nH]c2c1CN(N(C)CCOC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NCC1SC(=O)NC1=O)C2(C)C
Step 3: CYP3A4 ✅
| Original | New | Change |
|---|---|---|
| 0.000004 | 0.000001 | -0.000004 ↓ |
CCCCCCC(CCCC)COC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)Nc1n[nH]c2c1CN(N(C)CCOC(=O)[C@@H](Cc1cc(Br)c(O)c(Br)c1)NCC1SC(=O)NC1=O)C2(C)C
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.408545 | 0.155246 | -0.253299 | +0.6200 | -62.00% | ✅ Improved |
| BBBP | ↑ higher | 0.646056 | 1.000000 | +0.353944 | +0.5479 | +54.79% | ✅ Improved |
| CYP3A4 | ↓ lower | 0.080225 | 0.000001 | -0.080224 | +1.0000 | -100.00% | ✅ Improved |
| DILI | ↓ lower | 0.804278 | 0.306504 | -0.497774 | +0.6189 | -61.89% | ✅ Improved |
| HIA | ↑ higher | 0.998374 | 1.000000 | +0.001626 | +0.0016 | +0.16% | ✅ Improved |
| PGP | ↓ lower | 0.538867 | 0.882034 | +0.343167 | -0.6368 | +63.68% | ❌ Declined |
Improved: 5/6 (83.3%) | Molecules: 373 | Paths: 7117
Status: 5/6 meet thresholds
⚠️ Below threshold: 1
| Task | Score | Threshold | Gap |
|---|---|---|---|
| PGP | 0.8820 | ↓ 0.3 | 0.5820 |
✅ Passing: 5
| Task | Score | Threshold |
|---|---|---|
| AMES | 0.1552 | ↓ 0.3 |
| BBBP | 1.0000 | ↑ 0.5 |
| CYP3A4 | 0.0000 | ↓ 0.55 |
| DILI | 0.3065 | ↓ 0.4 |
| HIA | 1.0000 | ↑ 0.2 |
Initial Task: BBBP
SMILES: CC1=C2[C@H](C(=O)[C@]3(C)[C@H](C[C@@H]4[C@@](CO4)([C@@]3(C)[C@@H]([C@](C[C@@H]1OC(=O)[C@@H]([C@H](C5=CC=CC=C5)NC(=O)C6=CC=CC=C6)O)(C2(C)C)O)OC(=O)C7=CC=CC=C7)OC(=O)C)O)OC(=O)C
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`CC1=C2[C@H](C(=O)[C@]3(C)[C@H](C[C@@H]4[C@@](CO4)([C@@]3(C)[C@@H]([C@](C[C@@H]1OC(=O)[C@@H]([C@H](C5=CC=CC=C5)NC(=O)C6=CC=CC=C6)O)(C2(C)C)O)OC(=O)C7=CC=CC=C7)OC(=O)C)O)OC(=O)C`
▶ Show ADMET Scores
|
**Final Optimized**
`CC(=O)O[C@H](CCl)CON[C@@H](c1ccccc1)[C@@H](O)C(=O)N1Cc2c(N[C@H](Cc3cc(Br)c(O)c(Br)c3)C(=O)OC[C@@H](CCl)OC(C)=O)n[nH]c2C1(C)C`
▶ Show ADMET Scores
|
Optimization Steps:
DETAILSPLACEHOLDER82
After (Step 1)
CC(=O)O[C@H](CCl)CON[C@@H](c1ccccc1)[C@@H](O)C(=O)O[C@H]1C[C@@]2(O)[C@@H](ON[C@H](Cc3cc(Br)c(O)c(Br)c3)C(=O)c3ccoc3C)[C@]3(C)[C@]4(OC(C)=O)CO[C@@H]4C[C@H](O)[C@@]3(C)C(=O)[C@H](OC(C)=O)C(=C1C)C2(C)C
QED: 0.0210 (-0.1070) ❌
Number of Blocks: 4 (+0) ➡️
Block Changes: 7 (+4, -3)
BBBP Score: 0.000153 → 0.000113 (-0.000040)
DETAILSPLACEHOLDER83
DETAILSPLACEHOLDER84
After (Step 2)
CC(=O)O[C@H](CCl)CON[C@@H](c1ccccc1)[C@@H](O)C(=O)N1Cc2c(N[C@H](Cc3cc(Br)c(O)c(Br)c3)C(=O)CC3SC(=O)NC3=O)n[nH]c2C1(C)C
QED: 0.0672 (+0.0462) ✅
Number of Blocks: 5 (+1) ↑
Block Changes: 3 (+2, -1)
AMES Score: 0.677737 → 0.576776 (-0.100962)
DETAILSPLACEHOLDER85
DETAILSPLACEHOLDER86
After (Step 3)
CC(=O)O[C@H](CCl)CON[C@@H](c1ccccc1)[C@@H](O)C(=O)N1Cc2c(N[C@H](Cc3cc(Br)c(O)c(Br)c3)C(=O)OC[C@@H](CCl)OC(C)=O)n[nH]c2C1(C)C
QED: 0.0507 (-0.0165) ❌
Number of Blocks: 5 (+0) ➡️
Block Changes: 8 (+4, -4)
AMES Score: 0.576776 → 0.233688 (-0.343087)
DETAILSPLACEHOLDER87
Step 1: BBBP ⚠️
| Original | New | Change |
|---|---|---|
| 0.000153 | 0.000113 | -0.000040 ↑ |
CC(=O)O[C@H](CCl)CON[C@@H](c1ccccc1)[C@@H](O)C(=O)O[C@H]1C[C@@]2(O)[C@@H](ON[C@H](Cc3cc(Br)c(O)c(Br)c3)C(=O)c3ccoc3C)[C@]3(C)[C@]4(OC(C)=O)CO[C@@H]4C[C@H](O)[C@@]3(C)C(=O)[C@H](OC(C)=O)C(=C1C)C2(C)C
Step 2: AMES ✅
| Original | New | Change |
|---|---|---|
| 0.677737 | 0.576776 | -0.100962 ↓ |
CC(=O)O[C@H](CCl)CON[C@@H](c1ccccc1)[C@@H](O)C(=O)N1Cc2c(N[C@H](Cc3cc(Br)c(O)c(Br)c3)C(=O)CC3SC(=O)NC3=O)n[nH]c2C1(C)C
Step 3: AMES ✅
| Original | New | Change |
|---|---|---|
| 0.576776 | 0.233688 | -0.343087 ↓ |
CC(=O)O[C@H](CCl)CON[C@@H](c1ccccc1)[C@@H](O)C(=O)N1Cc2c(N[C@H](Cc3cc(Br)c(O)c(Br)c3)C(=O)OC[C@@H](CCl)OC(C)=O)n[nH]c2C1(C)C
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.766300 | 0.233688 | -0.532611 | +0.6950 | -69.50% | ✅ Improved |
| BBBP | ↑ higher | 0.000153 | 1.000000 | +0.999847 | +6552.6969 | +655269.69% | ✅ Improved |
| CYP3A4 | ↓ lower | 0.009794 | 0.001079 | -0.008715 | +0.8899 | -88.99% | ✅ Improved |
| DILI | ↓ lower | 0.767576 | 0.459665 | -0.307911 | +0.4011 | -40.11% | ✅ Improved |
| HIA | ↑ higher | 0.750817 | 0.999811 | +0.248993 | +0.3316 | +33.16% | ✅ Improved |
| PGP | ↓ lower | 0.573305 | 0.862906 | +0.289601 | -0.5051 | +50.51% | ❌ Declined |
Improved: 5/6 (83.3%) | Molecules: 187 | Paths: 2468
Status: 4/6 meet thresholds
⚠️ Below threshold: 2
| Task | Score | Threshold | Gap |
|---|---|---|---|
| PGP | 0.8629 | ↓ 0.3 | 0.5629 |
| DILI | 0.4597 | ↓ 0.4 | 0.0597 |
✅ Passing: 4
| Task | Score | Threshold |
|---|---|---|
| AMES | 0.2337 | ↓ 0.3 |
| BBBP | 1.0000 | ↑ 0.5 |
| CYP3A4 | 0.0011 | ↓ 0.55 |
| HIA | 0.9998 | ↑ 0.2 |
Initial Task: CYP3A4
SMILES: CC(C)[C@H]1C2=CC=C(C=C2CC[C@@]1(CCN(C)CCCC3=NC4=C(C=CC=C4)N3)OC(=O)COC)F
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`CC(C)[C@H]1C2=CC=C(C=C2CC[C@@]1(CCN(C)CCCC3=NC4=C(C=CC=C4)N3)OC(=O)COC)F`
▶ Show ADMET Scores
|
**Final Optimized**
`Cc1ccc(C(=O)[C@@H](Cc2cc(Br)c(O)c(Br)c2)Nc2n[nH]c3c2CN(c2n[nH]c4c2CN(c2ccc(C#N)cc2F)C4(C)C)C3(C)C)s1`
▶ Show ADMET Scores
|
Optimization Steps:
DETAILSPLACEHOLDER90
After (Step 1)
Cc1nc(Nc2n[nH]c3c2CN(CCCN(C)CC[C@@]2(Oc4ccc(C#N)cc4F)CCc4cc(F)ccc4[C@@H]2C(C)C)C3(C)C)c2sccc2n1
QED: 0.1319 (-0.2353) ❌
Number of Blocks: 3 (+0) ➡️
Block Changes: 6 (+3, -3)
CYP3A4 Score: 0.020786 → 0.012962 (-0.007824)
DETAILSPLACEHOLDER91
DETAILSPLACEHOLDER92
After (Step 2)
Cc1nc(Nc2n[nH]c3c2CN(c2n[nH]c4c2CN(c2ccc(C#N)cc2F)C4(C)C)C3(C)C)c2sccc2n1
QED: 0.2579 (+0.1260) ✅
Number of Blocks: 4 (+1) ↑
Block Changes: 2 (+1, -1)
AMES Score: 0.735399 → 0.746586 (+0.011187)
DETAILSPLACEHOLDER93
DETAILSPLACEHOLDER94
After (Step 3)
Cc1ccc(C(=O)[C@@H](Cc2cc(Br)c(O)c(Br)c2)Nc2n[nH]c3c2CN(c2n[nH]c4c2CN(c2ccc(C#N)cc2F)C4(C)C)C3(C)C)s1
QED: 0.1154 (-0.1425) ❌
Number of Blocks: 5 (+1) ↑
Block Changes: 3 (+2, -1)
CYP3A4 Score: 0.000895 → 0.000141 (-0.000755)
DETAILSPLACEHOLDER95
Step 1: CYP3A4 ✅
| Original | New | Change |
|---|---|---|
| 0.020786 | 0.012962 | -0.007824 ↓ |
Cc1nc(Nc2n[nH]c3c2CN(CCCN(C)CC[C@@]2(Oc4ccc(C#N)cc4F)CCc4cc(F)ccc4[C@@H]2C(C)C)C3(C)C)c2sccc2n1
Step 2: AMES ⚠️
| Original | New | Change |
|---|---|---|
| 0.735399 | 0.746586 | +0.011187 ↓ |
Cc1nc(Nc2n[nH]c3c2CN(c2n[nH]c4c2CN(c2ccc(C#N)cc2F)C4(C)C)C3(C)C)c2sccc2n1
Step 3: CYP3A4 ✅
| Original | New | Change |
|---|---|---|
| 0.000895 | 0.000141 | -0.000755 ↓ |
Cc1ccc(C(=O)[C@@H](Cc2cc(Br)c(O)c(Br)c2)Nc2n[nH]c3c2CN(c2n[nH]c4c2CN(c2ccc(C#N)cc2F)C4(C)C)C3(C)C)s1
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.456651 | 0.665578 | +0.208928 | -0.4575 | +45.75% | ❌ Declined |
| BBBP | ↑ higher | 0.999996 | 0.000031 | -0.999965 | -1.0000 | -100.00% | ❌ Declined |
| CYP3A4 | ↓ lower | 0.020786 | 0.000141 | -0.020645 | +0.9932 | -99.32% | ✅ Improved |
| DILI | ↓ lower | 0.675483 | 0.393913 | -0.281570 | +0.4168 | -41.68% | ✅ Improved |
| HIA | ↑ higher | 0.994189 | 0.999665 | +0.005475 | +0.0055 | +0.55% | ✅ Improved |
| PGP | ↓ lower | 0.700888 | 0.747508 | +0.046620 | -0.0665 | +6.65% | ❌ Declined |
Improved: 3/6 (50.0%) | Molecules: 283 | Paths: 5578
Status: 3/6 meet thresholds
⚠️ Below threshold: 3
| Task | Score | Threshold | Gap |
|---|---|---|---|
| BBBP | 0.0000 | ↑ 0.5 | 0.5000 |
| PGP | 0.7475 | ↓ 0.3 | 0.4475 |
| AMES | 0.6656 | ↓ 0.3 | 0.3656 |
✅ Passing: 3
| Task | Score | Threshold |
|---|---|---|
| CYP3A4 | 0.0001 | ↓ 0.55 |
| DILI | 0.3939 | ↓ 0.4 |
| HIA | 0.9997 | ↑ 0.2 |
Initial Task: CYP3A4
SMILES: CCC1=NN(CCCN2CCN(CC2)C3=CC=CC(=C3)Cl)C(=O)N1CCOC4=CC=CC=C4
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`CCC1=NN(CCCN2CCN(CC2)C3=CC=CC(=C3)Cl)C(=O)N1CCOC4=CC=CC=C4`
▶ Show ADMET Scores
|
**Final Optimized**
`CC1(C)c2[nH]nc(C(=O)c3ccc(Br)o3)c2CN1OCCCS(C)(=O)=O`
▶ Show ADMET Scores
|
Optimization Steps:
DETAILSPLACEHOLDER98
After (Step 1)
CS(=O)(=O)CCCOCC1SC(=O)NC1=O
QED: 0.6697 (+0.2155) ✅
Number of Blocks: 1 (-1) ↓
Block Changes: 3 (+1, -2)
CYP3A4 Score: 0.024539 → 0.001181 (-0.023358)
DETAILSPLACEHOLDER99
DETAILSPLACEHOLDER100
After (Step 2)
CS(=O)(=O)CCCONCc1ccc(/C(N)=N\O)cc1
QED: 0.2082 (-0.4615) ❌
Number of Blocks: 2 (+1) ↑
Block Changes: 3 (+2, -1)
AMES Score: 0.243126 → 0.686480 (+0.443354)
DETAILSPLACEHOLDER101
DETAILSPLACEHOLDER102
After (Step 3)
CC1(C)c2[nH]nc(C(=O)c3ccc(Br)o3)c2CN1OCCCS(C)(=O)=O
QED: 0.5145 (+0.3062) ✅
Number of Blocks: 1 (-1) ↓
Block Changes: 3 (+1, -2)
PGP Score: 0.675115 → 0.841080 (+0.165965)
DETAILSPLACEHOLDER103
Step 1: CYP3A4 ✅
| Original | New | Change |
|---|---|---|
| 0.024539 | 0.001181 | -0.023358 ↓ |
CS(=O)(=O)CCCOCC1SC(=O)NC1=O
Step 2: AMES ⚠️
| Original | New | Change |
|---|---|---|
| 0.243126 | 0.686480 | +0.443354 ↓ |
CS(=O)(=O)CCCONCc1ccc(/C(N)=N\O)cc1
Step 3: PGP ⚠️
| Original | New | Change |
|---|---|---|
| 0.675115 | 0.841080 | +0.165965 ↓ |
CC1(C)c2[nH]nc(C(=O)c3ccc(Br)o3)c2CN1OCCCS(C)(=O)=O
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.373806 | 0.284693 | -0.089113 | +0.2384 | -23.84% | ✅ Improved |
| BBBP | ↑ higher | 0.988244 | 1.000000 | +0.011756 | +0.0119 | +1.19% | ✅ Improved |
| CYP3A4 | ↓ lower | 0.024539 | 0.000204 | -0.024335 | +0.9917 | -99.17% | ✅ Improved |
| DILI | ↓ lower | 0.803705 | 0.390386 | -0.413319 | +0.5143 | -51.43% | ✅ Improved |
| HIA | ↑ higher | 0.999946 | 0.999757 | -0.000189 | -0.0002 | -0.02% | ❌ Declined |
| PGP | ↓ lower | 0.605185 | 0.841080 | +0.235895 | -0.3898 | +38.98% | ❌ Declined |
Improved: 4/6 (66.7%) | Molecules: 301 | Paths: 7666
Status: 5/6 meet thresholds
⚠️ Below threshold: 1
| Task | Score | Threshold | Gap |
|---|---|---|---|
| PGP | 0.8411 | ↓ 0.3 | 0.5411 |
✅ Passing: 5
| Task | Score | Threshold |
|---|---|---|
| AMES | 0.2847 | ↓ 0.3 |
| BBBP | 1.0000 | ↑ 0.5 |
| CYP3A4 | 0.0002 | ↓ 0.55 |
| DILI | 0.3904 | ↓ 0.4 |
| HIA | 0.9998 | ↑ 0.2 |
Initial Task: HIA
SMILES: O=C(N/C1=C/C2=CC=C3N=CC=C(C4=CC=NC=C4)C3=C2)SC1=O
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`O=C(N/C1=C/C2=CC=C3N=CC=C(C4=CC=NC=C4)C3=C2)SC1=O`
▶ Show ADMET Scores
|
**Final Optimized**
`CC1(C)c2[nH]nc(C(=O)Cc3cccs3)c2CN1c1n[nH]c2c1CN(c1ccnc3ccc(C=C4NC(=O)SC4=O)cc13)C2(C)C`
▶ Show ADMET Scores
|
Optimization Steps:
DETAILSPLACEHOLDER106
After (Step 1)
O=C1NC(=Cc2ccc3nccc(C=C4NC(=O)SC4=O)c3c2)C(=O)S1
QED: 0.7683 (+0.0430) ✅
Number of Blocks: 3 (+0) ➡️
Block Changes: 3 (+1, -2)
HIA Score: 0.885416 → 0.992403 (+0.106986)
DETAILSPLACEHOLDER107
DETAILSPLACEHOLDER108
After (Step 2)
CC1(C)c2[nH]nc(C(=O)Cc3cccs3)c2CN1c1ccnc2ccc(C=C3NC(=O)SC3=O)cc12
QED: 0.2837 (-0.4847) ❌
Number of Blocks: 4 (+1) ↑
Block Changes: 2 (+2, -0)
PGP Score: 0.675779 → 0.597692 (-0.078087)
DETAILSPLACEHOLDER109
DETAILSPLACEHOLDER110
After (Step 3)
CC1(C)c2[nH]nc(C(=O)Cc3cccs3)c2CN1c1n[nH]c2c1CN(c1ccnc3ccc(C=C4NC(=O)SC4=O)cc13)C2(C)C
QED: 0.1491 (-0.1346) ❌
Number of Blocks: 5 (+1) ↑
Block Changes: 1 (+1, -0)
PGP Score: 0.597692 → 0.561292 (-0.036400)
DETAILSPLACEHOLDER111
Step 1: HIA ✅
| Original | New | Change |
|---|---|---|
| 0.885416 | 0.992403 | +0.106986 ↑ |
O=C1NC(=Cc2ccc3nccc(C=C4NC(=O)SC4=O)c3c2)C(=O)S1
Step 2: PGP ✅
| Original | New | Change |
|---|---|---|
| 0.675779 | 0.597692 | -0.078087 ↓ |
CC1(C)c2[nH]nc(C(=O)Cc3cccs3)c2CN1c1ccnc2ccc(C=C3NC(=O)SC3=O)cc12
Step 3: PGP ✅
| Original | New | Change |
|---|---|---|
| 0.597692 | 0.561292 | -0.036400 ↓ |
CC1(C)c2[nH]nc(C(=O)Cc3cccs3)c2CN1c1n[nH]c2c1CN(c1ccnc3ccc(C=C4NC(=O)SC4=O)cc13)C2(C)C
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.729690 | 0.701288 | -0.028402 | +0.0389 | -3.89% | ✅ Improved |
| BBBP | ↑ higher | 0.001116 | 0.000159 | -0.000957 | -0.8576 | -85.76% | ❌ Declined |
| CYP3A4 | ↓ lower | 0.017947 | 0.003058 | -0.014888 | +0.8296 | -82.96% | ✅ Improved |
| DILI | ↓ lower | 0.885647 | 0.648698 | -0.236948 | +0.2675 | -26.75% | ✅ Improved |
| HIA | ↑ higher | 0.885416 | 0.974224 | +0.088808 | +0.1003 | +10.03% | ✅ Improved |
| PGP | ↓ lower | 0.542834 | 0.561292 | +0.018458 | -0.0340 | +3.40% | ❌ Declined |
Improved: 4/6 (66.7%) | Molecules: 67 | Paths: 88
Status: 2/6 meet thresholds
⚠️ Below threshold: 4
| Task | Score | Threshold | Gap |
|---|---|---|---|
| BBBP | 0.0002 | ↑ 0.5 | 0.4998 |
| AMES | 0.7013 | ↓ 0.3 | 0.4013 |
| PGP | 0.5613 | ↓ 0.3 | 0.2613 |
| DILI | 0.6487 | ↓ 0.4 | 0.2487 |
✅ Passing: 2
| Task | Score | Threshold |
|---|---|---|
| CYP3A4 | 0.0031 | ↓ 0.55 |
| HIA | 0.9742 | ↑ 0.2 |
Initial Task: HIA
SMILES: O=c1ncn2nc(Sc3ccccc3)ccc2c1-c1c(Cl)cccc1Cl
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`O=c1ncn2nc(Sc3ccccc3)ccc2c1-c1c(Cl)cccc1Cl`
▶ Show ADMET Scores
|
**Final Optimized**
`CC1(C)c2[nH]nc(N3Cc4c(C(=O)Cc5cccs5)n[nH]c4C3(C)C)c2CN1C=C1NC(=O)SC1=O`
▶ Show ADMET Scores
|
Optimization Steps:
DETAILSPLACEHOLDER114
After (Step 1)
O=C1NC(=CCC2SC(=O)NC2=O)C(=O)S1
QED: 0.7044 (+0.2309) ✅
Number of Blocks: 2 (+0) ➡️
Block Changes: 4 (+2, -2)
HIA Score: 0.988214 → 1.000000 (+0.011786)
DETAILSPLACEHOLDER115
DETAILSPLACEHOLDER116
After (Step 2)
CC(C)COc1n[nH]c2c1CN(C=C1NC(=O)SC1=O)C2(C)C
QED: 0.8206 (+0.1163) ✅
Number of Blocks: 2 (+0) ➡️
Block Changes: 2 (+1, -1)
PGP Score: 0.675575 → 0.621777 (-0.053797)
DETAILSPLACEHOLDER117
DETAILSPLACEHOLDER118
After (Step 3)
CC1(C)c2[nH]nc(N3Cc4c(C(=O)Cc5cccs5)n[nH]c4C3(C)C)c2CN1C=C1NC(=O)SC1=O
QED: 0.3409 (-0.4797) ❌
Number of Blocks: 4 (+2) ↑
Block Changes: 4 (+3, -1)
PGP Score: 0.621777 → 0.627767 (+0.005990)
DETAILSPLACEHOLDER119
Step 1: HIA ✅
| Original | New | Change |
|---|---|---|
| 0.988214 | 1.000000 | +0.011786 ↑ |
O=C1NC(=CCC2SC(=O)NC2=O)C(=O)S1
Step 2: PGP ✅
| Original | New | Change |
|---|---|---|
| 0.675575 | 0.621777 | -0.053797 ↓ |
CC(C)COc1n[nH]c2c1CN(C=C1NC(=O)SC1=O)C2(C)C
Step 3: PGP ⚠️
| Original | New | Change |
|---|---|---|
| 0.621777 | 0.627767 | +0.005990 ↓ |
CC1(C)c2[nH]nc(N3Cc4c(C(=O)Cc5cccs5)n[nH]c4C3(C)C)c2CN1C=C1NC(=O)SC1=O
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.675174 | 0.314901 | -0.360274 | +0.5336 | -53.36% | ✅ Improved |
| BBBP | ↑ higher | 0.000046 | 0.999992 | +0.999947 | +21894.4005 | +2189440.05% | ✅ Improved |
| CYP3A4 | ↓ lower | 0.002328 | 0.006490 | +0.004162 | -1.7876 | +178.76% | ❌ Declined |
| DILI | ↓ lower | 0.771123 | 0.495032 | -0.276091 | +0.3580 | -35.80% | ✅ Improved |
| HIA | ↑ higher | 0.988214 | 0.999245 | +0.011031 | +0.0112 | +1.12% | ✅ Improved |
| PGP | ↓ lower | 0.672094 | 0.627767 | -0.044327 | +0.0660 | -6.60% | ✅ Improved |
Improved: 5/6 (83.3%) | Molecules: 49 | Paths: 127
Status: 3/6 meet thresholds
⚠️ Below threshold: 3
| Task | Score | Threshold | Gap |
|---|---|---|---|
| PGP | 0.6278 | ↓ 0.3 | 0.3278 |
| DILI | 0.4950 | ↓ 0.4 | 0.0950 |
| AMES | 0.3149 | ↓ 0.3 | 0.0149 |
✅ Passing: 3
| Task | Score | Threshold |
|---|---|---|
| BBBP | 1.0000 | ↑ 0.5 |
| CYP3A4 | 0.0065 | ↓ 0.55 |
| HIA | 0.9992 | ↑ 0.2 |
Initial Task: CYP3A4
SMILES: O=C1N=C(CC(N2[C@@H](C)CC3=C2C=CC=C3)=O)NC(N4CCOCC4)=C1
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`O=C1N=C(CC(N2[C@@H](C)CC3=C2C=CC=C3)=O)NC(N4CCOCC4)=C1`
▶ Show ADMET Scores
|
**Final Optimized**
`CC1(C)c2[nH]nc(N3Cc4c(C(=O)Cc5cccs5)n[nH]c4C3(C)C)c2CN1C=C1NC(=O)SC1=O`
▶ Show ADMET Scores
|
Optimization Steps:
DETAILSPLACEHOLDER122
After (Step 1)
O=C1NC(=Cc2nc(=O)cc(N3CCOCC3)[nH]2)C(=O)S1
QED: 0.7369 (-0.1570) ❌
Number of Blocks: 2 (+0) ➡️
Block Changes: 2 (+1, -1)
CYP3A4 Score: 0.038089 → 0.034567 (-0.003522)
DETAILSPLACEHOLDER123
DETAILSPLACEHOLDER124
After (Step 2)
CC(C)COc1n[nH]c2c1CN(C=C1NC(=O)SC1=O)C2(C)C
QED: 0.8206 (+0.0838) ✅
Number of Blocks: 2 (+0) ➡️
Block Changes: 2 (+1, -1)
PGP Score: 0.755234 → 0.621777 (-0.133457)
DETAILSPLACEHOLDER125
DETAILSPLACEHOLDER126
After (Step 3)
CC1(C)c2[nH]nc(N3Cc4c(C(=O)Cc5cccs5)n[nH]c4C3(C)C)c2CN1C=C1NC(=O)SC1=O
QED: 0.3409 (-0.4797) ❌
Number of Blocks: 4 (+2) ↑
Block Changes: 4 (+3, -1)
PGP Score: 0.621777 → 0.627767 (+0.005990)
DETAILSPLACEHOLDER127
Step 1: CYP3A4 ✅
| Original | New | Change |
|---|---|---|
| 0.038089 | 0.034567 | -0.003522 ↓ |
O=C1NC(=Cc2nc(=O)cc(N3CCOCC3)[nH]2)C(=O)S1
Step 2: PGP ✅
| Original | New | Change |
|---|---|---|
| 0.755234 | 0.621777 | -0.133457 ↓ |
CC(C)COc1n[nH]c2c1CN(C=C1NC(=O)SC1=O)C2(C)C
Step 3: PGP ⚠️
| Original | New | Change |
|---|---|---|
| 0.621777 | 0.627767 | +0.005990 ↓ |
CC1(C)c2[nH]nc(N3Cc4c(C(=O)Cc5cccs5)n[nH]c4C3(C)C)c2CN1C=C1NC(=O)SC1=O
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.476903 | 0.314900 | -0.162003 | +0.3397 | -33.97% | ✅ Improved |
| BBBP | ↑ higher | 0.999998 | 0.999992 | -0.000006 | -0.0000 | -0.00% | ❌ Declined |
| CYP3A4 | ↓ lower | 0.038089 | 0.006490 | -0.031599 | +0.8296 | -82.96% | ✅ Improved |
| DILI | ↓ lower | 0.767693 | 0.495032 | -0.272661 | +0.3552 | -35.52% | ✅ Improved |
| HIA | ↑ higher | 0.999400 | 0.999245 | -0.000155 | -0.0002 | -0.02% | ❌ Declined |
| PGP | ↓ lower | 0.680634 | 0.627767 | -0.052867 | +0.0777 | -7.77% | ✅ Improved |
Improved: 4/6 (66.7%) | Molecules: 55 | Paths: 94
Status: 3/6 meet thresholds
⚠️ Below threshold: 3
| Task | Score | Threshold | Gap |
|---|---|---|---|
| PGP | 0.6278 | ↓ 0.3 | 0.3278 |
| DILI | 0.4950 | ↓ 0.4 | 0.0950 |
| AMES | 0.3149 | ↓ 0.3 | 0.0149 |
✅ Passing: 3
| Task | Score | Threshold |
|---|---|---|
| BBBP | 1.0000 | ↑ 0.5 |
| CYP3A4 | 0.0065 | ↓ 0.55 |
| HIA | 0.9992 | ↑ 0.2 |
Initial Task: DILI
SMILES: C[C@@H]([C@@H](CC1=CC=C(C=C1)Cl)C2=CC=CC(=C2)C#N)NC(=O)C(C)(C)OC3=NC=C(C=C3)C(F)(F)F
No valid paths found. The optimization could not generate any improved molecules.
Input SMILES: C[C@@H]([C@@H](CC1=CC=C(C=C1)Cl)C2=CC=CC(=C2)C#N)NC(=O)C(C)(C)OC3=NC=C(C=C3)C(F)(F)F
Reason: All generated molecules had worse scores than the initial molecule.
num_beams=7 or num_beams=10 for more diversitydepth=1 to see if single-step improvements workInitial Task: BBBP
SMILES: CC(C)(C)[N+]([O-])=Cc1ccc(cc1S(=O)(=O)[O-])S(=O)(=O)[O-].[Na+].[Na+]
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`CC(C)(C)[N+]([O-])=Cc1ccc(cc1S(=O)(=O)[O-])S(=O)(=O)[O-].[Na+].[Na+]`
▶ Show ADMET Scores
|
**Final Optimized**
`Cc1occc1-c1n[nH]c2c1CN(C=C1NC(=O)SC1=O)C2(C)C`
▶ Show ADMET Scores
|
Optimization Steps:
DETAILSPLACEHOLDER130
After (Step 1)
Cn1cc(C=C2NC(=O)SC2=O)c2ccccc21
QED: 0.7995 (+0.6727) ✅
Number of Blocks: 2 (-1) ↓
Block Changes: 4 (+2, -2)
BBBP Score: 0.001933 → 0.998710 (+0.996778)
DETAILSPLACEHOLDER131
DETAILSPLACEHOLDER132
After (Step 2)
O=C1NC(=CC=C2NC(=O)SC2=O)C(=O)S1
QED: 0.6715 (-0.1280) ❌
Number of Blocks: 2 (+0) ➡️
Block Changes: 1 (+0, -1)
AMES Score: 0.324786 → 0.209113 (-0.115673)
DETAILSPLACEHOLDER133
DETAILSPLACEHOLDER134
After (Step 3)
Cc1occc1-c1n[nH]c2c1CN(C=C1NC(=O)SC1=O)C2(C)C
QED: 0.8142 (+0.1427) ✅
Number of Blocks: 3 (+1) ↑
Block Changes: 2 (+2, -0)
PGP Score: 0.676219 → 0.583655 (-0.092563)
DETAILSPLACEHOLDER135
Step 1: BBBP ✅
| Original | New | Change |
|---|---|---|
| 0.001933 | 0.998710 | +0.996778 ↑ |
Cn1cc(C=C2NC(=O)SC2=O)c2ccccc21
Step 2: AMES ✅
| Original | New | Change |
|---|---|---|
| 0.324786 | 0.209113 | -0.115673 ↓ |
O=C1NC(=CC=C2NC(=O)SC2=O)C(=O)S1
Step 3: PGP ✅
| Original | New | Change |
|---|---|---|
| 0.676219 | 0.583655 | -0.092563 ↓ |
Cc1occc1-c1n[nH]c2c1CN(C=C1NC(=O)SC1=O)C2(C)C
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.531967 | 0.609732 | +0.077765 | -0.1462 | +14.62% | ❌ Declined |
| BBBP | ↑ higher | 0.001933 | 0.002764 | +0.000832 | +0.4304 | +43.04% | ✅ Improved |
| CYP3A4 | ↓ lower | 0.000120 | 0.004026 | +0.003907 | -32.6844 | +3268.44% | ❌ Declined |
| DILI | ↓ lower | 0.483893 | 0.741515 | +0.257622 | -0.5324 | +53.24% | ❌ Declined |
| HIA | ↑ higher | 0.994940 | 0.996004 | +0.001064 | +0.0011 | +0.11% | ✅ Improved |
| PGP | ↓ lower | 0.765508 | 0.583655 | -0.181853 | +0.2376 | -23.76% | ✅ Improved |
Improved: 3/6 (50.0%) | Molecules: 133 | Paths: 300
Status: 2/6 meet thresholds
⚠️ Below threshold: 4
| Task | Score | Threshold | Gap |
|---|---|---|---|
| BBBP | 0.0028 | ↑ 0.5 | 0.4972 |
| DILI | 0.7415 | ↓ 0.4 | 0.3415 |
| AMES | 0.6097 | ↓ 0.3 | 0.3097 |
| PGP | 0.5837 | ↓ 0.3 | 0.2837 |
✅ Passing: 2
| Task | Score | Threshold |
|---|---|---|
| CYP3A4 | 0.0040 | ↓ 0.55 |
| HIA | 0.9960 | ↑ 0.2 |
Initial Task: HIA
SMILES: CC(=O)N1CCN(CC1)CCOC2=CC=C(C=C2)C3CCN(CC3)C4=NN5C(=NN=C5C(F)(F)F)CC4
📊 Overall Comparison - Initial → Final
**Initial Molecule**
`CC(=O)N1CCN(CC1)CCOC2=CC=C(C=C2)C3CCN(CC3)C4=NN5C(=NN=C5C(F)(F)F)CC4`
▶ Show ADMET Scores
|
**Final Optimized**
`CC(C)(OC(=O)C(C)(C)OC1=Nn2c(nnc2C(F)(F)F)CC1)C(=O)NCc1ccc(/C(N)=N\O)cc1`
▶ Show ADMET Scores
|
Optimization Steps:
DETAILSPLACEHOLDER138
After (Step 1)
CC(=O)N1CCN(CCOC(=O)C(C)(C)OC2CCN(CC3=Nn4c(nnc4C(F)(F)F)CC3)CC2)CC1
QED: 0.4537 (-0.1511) ❌
Number of Blocks: 3 (-1) ↓
Block Changes: 3 (+1, -2)
HIA Score: 0.999712 → 0.999154 (-0.000558)
DETAILSPLACEHOLDER139
DETAILSPLACEHOLDER140
After (Step 2)
CC(C)(OC1CCN(CC2=Nn3c(nnc3C(F)(F)F)CC2)CC1)C(=O)NCc1ccc(/C(N)=N\O)cc1
QED: 0.2030 (-0.2507) ❌
Number of Blocks: 3 (+0) ➡️
Block Changes: 2 (+1, -1)
AMES Score: 0.396480 → 0.731145 (+0.334666)
DETAILSPLACEHOLDER141
DETAILSPLACEHOLDER142
After (Step 3)
CC(C)(OC(=O)C(C)(C)OC1=Nn2c(nnc2C(F)(F)F)CC1)C(=O)NCc1ccc(/C(N)=N\O)cc1
QED: 0.1621 (-0.0408) ❌
Number of Blocks: 3 (+0) ➡️
Block Changes: 4 (+2, -2)
AMES Score: 0.731145 → 0.641817 (-0.089329)
DETAILSPLACEHOLDER143
Step 1: HIA ⚠️
| Original | New | Change |
|---|---|---|
| 0.999712 | 0.999154 | -0.000558 ↑ |
CC(=O)N1CCN(CCOC(=O)C(C)(C)OC2CCN(CC3=Nn4c(nnc4C(F)(F)F)CC3)CC2)CC1
Step 2: AMES ⚠️
| Original | New | Change |
|---|---|---|
| 0.396480 | 0.731145 | +0.334666 ↓ |
CC(C)(OC1CCN(CC2=Nn3c(nnc3C(F)(F)F)CC2)CC1)C(=O)NCc1ccc(/C(N)=N\O)cc1
Step 3: AMES ✅
| Original | New | Change |
|---|---|---|
| 0.731145 | 0.641817 | -0.089329 ↓ |
CC(C)(OC(=O)C(C)(C)OC1=Nn2c(nnc2C(F)(F)F)CC1)C(=O)NCc1ccc(/C(N)=N\O)cc1
| Task | Direction | Initial | Final | Change | Rel. Improvement | % Change | Status |
|---|---|---|---|---|---|---|---|
| AMES | ↓ lower | 0.382188 | 0.641817 | +0.259629 | -0.6793 | +67.93% | ❌ Declined |
| BBBP | ↑ higher | 0.998411 | 0.000596 | -0.997815 | -0.9994 | -99.94% | ❌ Declined |
| CYP3A4 | ↓ lower | 0.030133 | 0.019928 | -0.010205 | +0.3387 | -33.87% | ✅ Improved |
| DILI | ↓ lower | 0.747011 | 0.551265 | -0.195746 | +0.2620 | -26.20% | ✅ Improved |
| HIA | ↑ higher | 0.999712 | 0.938515 | -0.061197 | -0.0612 | -6.12% | ❌ Declined |
| PGP | ↓ lower | 0.644132 | 0.620027 | -0.024105 | +0.0374 | -3.74% | ✅ Improved |
Improved: 3/6 (50.0%) | Molecules: 31 | Paths: 102
Status: 2/6 meet thresholds
⚠️ Below threshold: 4
| Task | Score | Threshold | Gap |
|---|---|---|---|
| BBBP | 0.0006 | ↑ 0.5 | 0.4994 |
| AMES | 0.6418 | ↓ 0.3 | 0.3418 |
| PGP | 0.6200 | ↓ 0.3 | 0.3200 |
| DILI | 0.5513 | ↓ 0.4 | 0.1513 |
✅ Passing: 2
| Task | Score | Threshold |
|---|---|---|
| CYP3A4 | 0.0199 | ↓ 0.55 |
| HIA | 0.9385 | ↑ 0.2 |